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3.5.4.25: GTP cyclohydrolase II

This is an abbreviated version!
For detailed information about GTP cyclohydrolase II, go to the full flat file.

Word Map on EC 3.5.4.25

Reaction

GTP
+ 4 H2O =
formate
+
2,5-diamino-6-hydroxy-4-(5-phospho-D-ribosylamino)pyrimidine
+ 2 phosphate

Synonyms

3,4-dihydroxy-2-butanone 4-phosphate synthase, GCH II, GCH II/III, GCH-II, gch2, GCHII, GTP 7,8-8,9-dihydrolase (diphosphate-forming), GTP cyclohydrolase 2, GTP cyclohydrolase II, GTP cyclohydrolase-II, GTP-8-formylhydrolase, GTPCH II, GTPCH-II, guanosine triphosphate cyclohydrolase II, guanosine triphosphate cyclohydrolase II/3,4-dihydroxy-2-butanone-4-phosphate synthase, guanosine-5'-triphosphate cyclohydrolase-II, More, NbRibA, ribA, ribA2, RIBIV, ToxB

ECTree

     3 Hydrolases
         3.5 Acting on carbon-nitrogen bonds, other than peptide bonds
             3.5.4 In cyclic amidines
                3.5.4.25 GTP cyclohydrolase II

Engineering

Engineering on EC 3.5.4.25 - GTP cyclohydrolase II

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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Y210C/A290T/Q293R/A296T/K322R/F339Y/M361I
-
the mutant shows a 2fold increase in GTP cyclohydrolase II activity and a 4fold increase in the Km value with GTP as the substrate. Using 2-amino-5-formylamino-6-ribosylamino-4(3H)-pyrimidinone 5'-triphosphate as the substrate, the mutant shows a rate enhancement by a factor of about 2 and an increase in the Km value by a factor of about 5
Y210C/A290T/Q293R/A296T/K322R/M361I
-
the mutant shows increased kcat and Km values compared to the wild type enzyme using GTP and 2-amino-5-formylamino-6-ribosylamino-4(3H)-pyrimidinone 5'-triphosphate as the substrate
C54S
-
site-directed mutagenesis, mutation results in proteins devoid of bound zinc and unable to release formate from the imidazole ring of GTP or from the intermediate analogue 2-amino-5-formylamino-6-ribosylamino-4(3H)-pyrimidinone 5'-triphosphate, however, the mutant enzyme is still capable to release diphosphate from GTP and from the formamide-type intermediate analogue
C65S
-
site-directed mutagenesis, mutation results in proteins devoid of bound zinc and unable to release formate from the imidazole ring of GTP or from the intermediate analogue 2-amino-5-formylamino-6-ribosylamino-4(3H)-pyrimidinone 5'-triphosphate, however, the mutant enzyme is still capable to release diphosphate from GTP and from the formamide-type intermediate analogue
C67S
-
site-directed mutagenesis, mutation results in proteins devoid of bound zinc and unable to release formate from the imidazole ring of GTP or from the intermediate analogue 2-amino-5-formylamino-6-ribosylamino-4(3H)-pyrimidinone 5'-triphosphate, however, the mutant enzyme is still capable to release diphosphate from GTP and from the formamide-type intermediate analogue
C396S
site-directed mutagenesis,
E154D
site-directed mutagenesis,
D127A
about 10fold less efficient than the wild-type protein
G209D
about 10fold less efficient than the wild-type protein
M120A
generated by site-directed mutagenesis
M120C
generated by site-directed mutagenesis
M120D
generated by site-directed mutagenesis
M120E
generated by site-directed mutagenesis
M120F
generated by site-directed mutagenesis
M120G
generated by site-directed mutagenesis
M120H
generated by site-directed mutagenesis
M120I
generated by site-directed mutagenesis
M120K
generated by site-directed mutagenesis
M120N
generated by site-directed mutagenesis
M120Q
generated by site-directed mutagenesis
M120S
generated by site-directed mutagenesis
M120T
generated by site-directed mutagenesis
M120W
generated by site-directed mutagenesis
M120Y
generated by site-directed mutagenesis
R83H
mutant substantially impaired in overall activity
Y123M
about 10fold less efficient than the wild-type protein, produces exclusively 2-amino-5-formylamino-6-ribosylamino-4(3H)-pyrimidinone 5'-phosphate
Y326F
generated by site-directed mutagenesis, catalytically inactive variant
Y326M
generated by site-directed mutagenesis, catalytically inactive variant
additional information